1. Cell Cycle/DNA Damage
    Stem Cell/Wnt
  2. Casein Kinase

IC261 

Cat. No.: HY-12774 Purity: 98.97%
Handling Instructions

IC261 is a selective, ATP-competitive CK1 inhibitor, with IC50s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively.

For research use only. We do not sell to patients.
IC261 Chemical Structure

IC261 Chemical Structure

CAS No. : 186611-52-9

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 119 In-stock
5 mg USD 108 In-stock
10 mg USD 192 In-stock
50 mg USD 816 In-stock
100 mg   Get quote  
200 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

IC261 is a selective, ATP-competitive CK1 inhibitor, with IC50s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively.

IC50 & Target

IC50: 1 μM (Ckiδ), 1 μM (Ckiε), 16 μM (Ckiα1)[1]

In Vitro

IC261 is a selective, ATP-competitive CK1 inhibitor, with IC50s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively. IC261 is less active on PKA, p34cdc2, and p55fyn (IC50s > 100 μM)[1]. IC261 induces mitotic arrest, spindle defects and centrosome amplification in AC1-M88 cells. IC261 (1 μM) increases G2/M cells after 12 h, and causes cell death at 24 h in AC1-M88 cells. IC261 (1 μM) also induces apoptosis in the extravillous trophoblast hybrid cells[2]. IC261 (1.25 μM) suppresses the proliferation of several pancreatic tumour cell lines, including ASPC-1, BxPc3, Capan-1, Colo357, MiaPaCa-2, Panc1, Panc89, PancTu-1 and PancTu-2 cells. IC261 (1.25 μM) specifically enhances CD95-mediated apoptosis of pancreatic tumour cells[3].

In Vivo

IC261 (20.5 mg/kg) inhibits tumor growth of PancTu-2 cells in SCID mice, downregulates several anti-apoptotic proteins, such as CK1δ/∊, KRAS, and IL6 and upregulates p21, ATM, CHEK1 and STAT1 in mice[3].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 3.2120 mL 16.0601 mL 32.1203 mL
5 mM 0.6424 mL 3.2120 mL 6.4241 mL
10 mM 0.3212 mL 1.6060 mL 3.2120 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

Casein kinase activity is assayed at 37°C. The standard reaction (40 μL) contains 25 mM 2-(N-morpholino)ethanesulfonic acid, pH 6.5, 50 mM NaCl, 15 mM MgCl2, 2 mg/mL casein, 2 mM EGTA, 100 μM [γ-32P]ATP (100-400 cpm/pmol). Initial velocity measurements are carried out in duplicate with ATP as the varied substrate. Kinetic constants and their standard errors are calculated. For assay of inhibitor potency (IC50), [γ -32P]ATP is held constant (10 μM), whereas IC261 concentration is varied (0.1, 0.3, 1, 3, and 10 μM). To assess kinetic mechanism, inhibitors are held constant (IC261, 20 μM; IC3608, 100 μM), whereas [γ -32P]ATP is varied as above. For screening small molecule libraries, CK1 isoforms (Ckiα1, δ, and ε) are assayed that casein is used at 10 mg/mL, [γ -32P]ATP is held constant at 2 μM or 1 mM[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

IC261 is dissolved in DMSO as a stock solution at 25 mM.

Human extravillous trophoblast cells irreversibly leave the cell cycle and die when isolated from its natural extracellular matrix. The cell line AC1-M88 is employed in vitro experiments. This cell line is generated by fusion of extravillous trophoblasts with AC1-1. Cells are grown in DMEM (CV-1) or DMEM/F-12 (AC1-M88) medium supplemented with 10% fetal calf serum (FCS) at 37°C in a humidified 5% CO2 atmosphere. Where indicated, cells are γ-irradiated with 5 Gy and harvested at the given time points for western blot analysis, treated with 1 μM IC261 or 0.4 μM nocodazole for 12 h and fixed for immunofluorescence analysis, or treated with 1 μM IC261 and fixed for flow cytometrical analysis or lysed for western blot analysis at the indicated time points. IC261 and nocodazole are dissolved in DMSO as stock solutions (25 and 10 mM, respectively), and control cells are treated with 0.004% DMSO. For immunocytochemistry, the cells are grown on coverslips and are treated with methanol (−20°C) for 5 min, followed by acetone (−20°C) for 20-30 s prior to being used for immunocytochemical detection[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[3]

IC261 is dissolved in DMSO.

Five million PancTu-1 cells resuspended in 100 µL of a solution containing 50% Matrigel and 50% DMEM/RPMI-1640 (1:1) are injected into the dorsolateral site of 6-week-old C.B-17/IcrHsd-scid-bg mice. After 17 days, mice are randomised to the control group (n = 5), the IC261 treatment group (n = 5), the gemcitabine group (n = 5) and to the IC261/gemcitabine group (n = 5). Injection of dimethylsulfoxide (DMSO; control group), IC261 (20.5 mg/kg), gemcitabine (0.6 mg/kg) alone or in combination (20.5 mg/kg IC261/0.6 mg/kg gemcitabine) (treatment groups) is performed daily for 8 days. Mice are sacrificed by asphyxiation with CO2 the day after the last treatment. Tumours are measured before and during treatment. Finally, the tumours are excised, measured, weighed and fixed in formalin or shock frozen. Tumour volume is calculated according to the formula for a rotational ellipsoid (length × height × width × 0.5236)[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

311.33

Formula

C₁₈H₁₇NO₄

CAS No.

186611-52-9

SMILES

O=C1NC2=C(C=CC=C2)/C1=C\C3=C(OC)C=C(OC)C=C3OC

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 33 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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IC261
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